The present research proposal aims to define the biochemical mechanisms involved in the interaction between antidiuretic hormone (vasopressin) and prostaglandins in the kidney. To circumvent the problem of tissue heterogeneity encountered in most previous studies, this interaction will be examined specifically in the collecting tubule microdissected from the inner medulla of the rat kidney. The specific aims of this proposal will be: 1) a) To determine the effects of inhibition of endogenous prostaglandin synthesis on vasopressin (AVP)-dependent cAMP formation in the collecting tubule, b) to determine the effects of hyperosmolality and specific solutes on prostaglandin synthesis in the collecting tubule and their implications for AVP-dependent cAMP formation, c) to assess the potential role of calcium in the interaction between prostaglandins and vasopressin. 2) To determine whether AVP stimulates prostaglandin synthesis in the collecting tubule, and if so, to determine the mechanism of stimulation. 3) To determine whether altered prostaglandin synthesis in the collecting tubule may be associated wih specific syndromes of impaired water excretion.